The incidence of major cardiovascular events in immigrants to Ontario, Canada:

The incidence of major cardiovascular events in immigrants to Ontario, Canada: The CANHEART Immigrant Study Jack V. Tu, Anna Chu, Mohammad R. Rezai, Helen Guo, Laura C. Maclagan, Peter C. Austin, Gillian L. Booth, Douglas G. Manuel, Maria Chiu, Dennis T. Ko, Douglas S. Lee, Baiju R. Shah, Linda R. Donovan, Qazi Z. Sohail, David A. Alter Circulation (Online before print August 31, 215) Institute for Clinical Evaluative Sciences

Background Global migration to high-income countries is increasing. Little is known about the incidence of cardiovascular diseases in migrant populations from different ethnic backgrounds and regions of the world. Previous studies have been primarily been conducted in Europe. (Dassanayake J, Asia-Pacific Journal of Public Health 211;23:882-95) Among high-income countries, Canada has one of the highest per-capita rates of immigration. Ontario, Canada represents an ideal setting in which to conduct research on cardiovascular diseases in multi-ethnic migrant populations. 2

Overall Objective To determine, in a large multi-ethnic cohort of firstgeneration immigrants who immigrated to Ontario between 1985 and 2, the: i. Prevalence of traditional cardiovascular risk factors and, ii. 1-year incidence rates of major cardiovascular events. 3

Methods Design Retrospective cohort study of 824,662 immigrants from 21 countries of birth. Identified from Citizenship and Immigration Canada s Permanent Resident database, linked to 9 population-based health databases. Inclusion/Exclusion Criteria All legal immigrants aged 3-74 years as of January 22, who landed in Ontario between 1985 and 2. No known history of a major cardiovascular event prior to January 22. Immigrants classified into 1 of 8 major ethnic groups, based upon their country of birth, mother tongue and surname. (Rezai M, Open Med 213; 7:85-93; Shah B, BMC Medical Research Methodology 21;1:42) White-Western European (including US, Australia, New Zealand), White-Eastern European, East Asian, Black, Southeast Asian, Latin American, West Asian/Arab (Middle East), South Asian. 4

Data Sources Socio-demographics: Citizenship and Immigration Canada (CIC) Permanent Resident Database Ontario Registered Persons Database Ontario Drug Benefits Claims Database Ontario Visible Minority Database Health care utilization: Ontario Health Insurance Plan Physician Claims Database CIHI Hospital Discharge Abstract Database* CVD risk factors: Canadian Community Health Survey (smoking, BMI) Ontario Hypertension Database Ontario Diabetes Database Gamma-Dynacare Medical Laboratories (lipids) STUDY COHORT 824,662 immigrants 5,2,258 long-term residents 3-74 years of age on January 1, 22 Clinical outcomes: CIHI Hospital Discharge Abstract Database* Registrar General of Ontario Vital Statistics Database * CIHI=Canadian Institute for Health Information Born in Canada or immigrated prior to 1985. 5

Primary Outcome Age-standardized 1-year incidence rate of a major cardiovascular event (22-211) Defined as a composite outcome consisting of: Acute myocardial infarction (AMI) Heart Attack Stroke Percutaneous coronary intervention (PCI) Coronary artery bypass graft surgery (CABG) Cardiovascular (CVD) death (All results standardized to the 26 Ontario census population) 6

Cardiac Risk Factor Score Purpose: To quantify the relative combined burden of four traditional modifiable cardiac risk factors smoking, diabetes, hypertension and hyperlipidemia. A points-based score using similar methods to those used in creating the Framingham risk score. (Sullivan LM, Statist Med 24;23:1631-6) Points for each risk factor are determined from β- coefficients from a multivariate Cox proportional hazards model. Higher scores = higher risk 7

Cardiac Risk Factor Score Points System Risk Factor Category Males Points Females Points Age (years) 3-34 -2-2 35-39 -1-1 4-44 45-49 1 1 5-54 2 2 55-59 3 3 6-64 4 4 65-69 5 5 7-74 6 6 Hypertension 1 1 Diabetes 2 2 Total cholesterol (mmol/l) < 4.14-1 4.14 5.15 5.16 6.19 6.2 7.22 1 1 7.23 2 1 HDL cholesterol (mmol/l) < 1.3 1 1 1.3 1.28 1.29 1.53-1 1.54-1 -1 Smoker 2 2 * Categories in bold are the reference categories. Total points range (minimum maximum) -4 to 14-3 to 13 8

Statistical Analyses Age-standardized 1-year incidence rates per 1 personyears follow-up were calculated using the 26 Ontario population aged 3 to 74 as the standard population. Sex-stratified analyses by country of birth for those 29 countries with at least 5 immigrants to Ontario. Pearson correlation coefficients to examine the association between the mean ethnic-group specific cardiac risk factor score and the ethnic-group specific incidence rate of cardiovascular events. Sex-stratified, sequential Cox proportional hazard modelling to investigate differences in the primary outcome between ethnic groups and the long-term resident cohort. 9

Study cohort includes immigrants from 21 countries of birth from around the world 1985-2 1

Baseline Characteristics of Immigrants (in order of CVD risk among males) Variable/ Ethnic Group Population size, n Age on arrival, years* Age on Jan 1, 22, years* East Asian Black White- Western European Southeast Asian Latin American West Asian/ Arab White- Eastern European South Asian All Immigrants 174,167 84,914 82,998 68,239 55,173 71,77 121,912 165,489 824,662 38 33 33 36 34 35 35 37 36 45 42 44 44 44 43 44 44 44 Females, %* 52 51 5 6 49 42 5 47 5 Completed university, % Immigration class, % Economic Family Refugee Years in Ontario (to Jan 1, 22) Country of birth income group High Middle Low 26 8 19 28 12 32 31 28 24 58 34 3 3 52 18 57 42 43 47 1 3 46 23 8.1 9.5 1.5 8.9 9.9 8.1 8.5 7.6 8.6 44 5 6 2 46 34 93 7 8 2 1 * Unadjusted results. All other results are age-/sex-standardized. Includes skilled workers, entrepreneurs, self-employed, live-in caregivers, investors and their dependents. 43 27 29 6 84 11 34 29 37 1 99 39 47 12 3 29 68 43 4 15 22 57 21 11

Risk factors Immigrants vs Long-term Residents* Risk Factors at Baseline (January 1, 22) All Immigrants Males Long-term Residents All Immigrants Females Long-term Residents Population size, n 412,875 2,484,554 411,787 2,715,74 Current cigarette smoker, % 24.5 28.7 8.6 23.8 Hypertension, % 17.9 2.6 2.3 21.3 Diabetes, % 8.8 7.3 8.2 6. Mean total cholesterol, mmol/l Mean HDL cholesterol, mmol/l Mean total to HDL cholesterol ratio 5.3 5.3 5.2 5.4 1.3 1.3 1.5 1.6 4.4 4.4 3.6 3.6 Body mass index, kg/m 2 25.6 27.2 24.7 26. Cardiac risk factor score 2.2 2.3 1.8 2.1 *All results are age-standardized. 12

Age-standardized prevalence of cardiovascular risk factors by ethnicity East Asian Black White-Western European Southeast Asian Latin American West Asian/Arab White-Eastern European South Asian Long-term Residents Males Females East Asian Black White-Western European Southeast Asian Latin American West Asian/Arab White-Eastern European South Asian Long-term Residents 1 2 3 4 5 Smoking Prevalence, % 5 1 15 2 25 3 35 Hypertension Prevalence, % East Asian Black White-Western European Southeast Asian Latin American West Asian/Arab White-Eastern European South Asian Long-term Residents East Asian Black White-Western European Southeast Asian Latin American West Asian/Arab White-Eastern European South Asian Long-term Residents 5 1 15 2 25 3 35 Diabetes Prevalence, % 2.5 3. 3.5 4. 4.5 5. Mean Total/HDL Cholesterol Ratio 13

Age-standardized incidence of a major cardiovascular event by ethnicity, 22-211* Males East Asian Black White-Western European Southeast Asian Latin American West Asian/Arab White-Eastern European South Asian All All immigrants Immigrants Long-term Residents residents 2.4 4.7 4.8 5.4 5.6 5.6 6.7 7.2 8.1 8.9 Females East Asian White-Western European Southeast Asian White-Eastern European Black Latin American West Asian/Arab South Asian All All immigrants Immigrants Long-term Residents residents 1.1 2.1 2.1 2.5 2.4 2.7 2.9 2.9 3.4 3.6. 2. 4. 6. 8. 1. Incidence rate, per 1 person-yrs *A major cardiovascular event includes AMI, stroke, PCI, CABG surgery or death due to IHD or stroke. 14

Incidence rate, per 1 person-years Incidence of a Major Cardiovascular Event by Duration of Residence - Males* 12 1 In Ontario <1 yrs In Ontario 1+ yrs 8 6 1% 4 4% 2 *AMI, stroke, PCI, CABG surgery or death due to IHD or stroke. All results are age-standardized. 15

Incidence rate, per 1 person-years Incidence of a Major Cardiovascular Event by Duration of Residence - Females* 5 4 In Ontario <1 yrs In Ontario 1+ yrs 3 1% 2 6% 1 *AMI, stroke, PCI, CABG surgery or death due to IHD or stroke. All results are age-standardized. 16

Age-standardized incidence of a major cardiovascular event by country and region of birth among 29 countries of birth with at least 5 immigrants, 22-211* Males Females East Asia Western Europe/ United States Sub-Saharan Africa/ Caribbean Southeast Asia Latin America Middle East/West Asia Eastern Europe South Asia Taiwan Hong Kong China South Korea United States Portugal United Kingdom Ghana Somalia Ethiopia Jamaica Trinidad & Tobago Vietnam Philippines El Salvador Guyana Iran Lebanon Egypt Afghanistan Iraq Romania Yugoslavia Russia Poland India Bangladesh Pakistan Sri Lanka Long-term Residents 2 4 6 8 1 12 Incidence, per 1 person-years (95% CI) Taiwan Hong Kong China South Korea United States Portugal United Kingdom Ethiopia Somalia Ghana Jamaica Trinidad & Tobago Vietnam Philippines El Salvador Guyana Lebanon Iran Egypt Iraq Afghanistan Romania Yugoslavia Russia Poland Sri Lanka India Pakistan Bangladesh Long-term Residents 2 4 6 8 1 12 Incidence, per 1 person-years (95% CI) *A major cardiovascular event includes AMI, stroke, PCI, CABG surgery or death due to IHD or stroke. 17

Incidence of a major cardiovascular event, per 1 person-years Incidence of a major cardiovascular event, per 1 person-years Incidence of a major cardiovascular event, per 1person-years Incidence of a major cardiovascular event, per 1person-years Age-standardized cardiac risk factor score versus incidence of a major cardiovascular event by ethnicity and country of birth, 22-211* 1 9 8 7 6 5 4 3 2 1 East Asian Males By ethnicity, R=.76 South Asian Long-term resident White-Eastern European West Asian Latin American Southeast Asian Black White-Western European 1. 1.2 1.4 1.6 1.8 2. 2.2 2.4 2.6 Mean cardiac risk factor score 4 3 2 1 Latin American Black White-Western European East Asian Females By ethnicity, R=.92 White-Eastern European South Asian Long-term resident West Asian Southeast Asian 1. 1.2 1.4 1.6 1.8 2. 2.2 Mean cardiac risk factor score 12 1 8 6 4 2 By country of birth, R=.81 Guyana Sri Lanka Pakistan Iraq Bangladesh Afghanistan Russia India Poland Trinidad & Tobago Yugoslavia Egypt United Kingdom Romania Iran Lebanon Philippines Portugal El Salvador Jamaica United States Vietnam Somalia Ethiopia South Korea Ghana China Hong Kong Taiwan 1. 1.5 2. 2.5 3. Mean cardiac risk factor score 7 6 5 By country of birth, R=.75 Afghanistan Iraq Guyana 4 Trinidad & Tobago Bangladesh Pakistan India Sri Lanka 3 Poland Jamaica United Kingdom Russia Yugoslavia Egypt Romania Iran Portugal 2 South Korea Vietnam Philippines El Salvador United States Lebanon Ethiopia Ghana Somalia 1 Hong Kong China Taiwan 1. 1.2 1.4 1.6 1.8 2. 2.2 2.4 Mean cardiac risk factor score *A major cardiovascular event includes AMI, stroke, PCI, CABG surgery or death due to IHD or stroke. 18

Adjusted relative risk of a major cardiovascular event by ethnicity compared with long-term residents, 22-211* Hazard Ratio (95% CI) Males East Asian.32 (.3,.34) Black.59 (.55,.64) White-Western European.61 (.57,.64) Southeast Asian.62 (.57,.68) Latin American.63 (.58,.67) West Asian/Arab.75 (.71,.8) White-Eastern European.83 (.79,.87) South Asian 1.2 (.99, 1.6) Long-term residents (ref) Females East Asian.38 (.35,.41) Southeast Asian.56 (.51,.61) White-Western European.68 (.62,.75) Latin American.71 (.65,.79) White-Eastern European.73 (.68,.78) Black.73 (.67,.79) West Asian/Arab.76 (.69,.85) South Asian.89 (.85,.93).25.5 1. 1.5 Hazard Ratio (95% CI) *Adjusted for age, income quintile, smoking, diabetes, hypertension, total cholesterol and HDL cholesterol. 19

Summary The 1-year incidence of major cardiovascular events is 3% lower in male and female immigrants as compared with long-term residents of Ontario. Striking 4-fold variation in event rates between immigrants from different ethnic backgrounds. Lower rates of smoking and obesity in most immigrant groups likely contribute to the healthy immigrant effect. East Asian immigrants have the lowest CVD event rates, but the rates increase dramatically with longer duration of residence in Canada. Immigrants of South Asian origin and those born in Iraq and Afghanistan have the highest risk of cardiovascular events. Variations in CVD event rates can be explained in part by variations in the burden of traditional cardiovascular risk factors but other factors (e.g. lifestyle, environment, genetics, etc.) also likely play an important role. 2

Funding Sources This study was supported by operating grants from: Public Health Agency of Canada Institute for Circulatory and Respiratory Health-Canadian Institutes of Health Research (ICRH-CIHR) Team Grant- Chronic Disease Risk and Intervention Strategies (#TCA 118349) CIHR operating grant (#MOP-11135) Heart and Stroke Foundation of Ontario (pilot grant) The opinions, results and conclusions reported in this paper are those of the authors and independent from the funding sources. 21

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